THE THERAPEUTIC POTENTIAL OF INCRETIN-BASED THERAPIES AND THE EMERGING ROLE OF METABOLIC MODULATION IN THE MANAGEMENT OF OBSTRUCTIVE SLEEP APNEA: A MECHANISTIC AND CLINICAL REVIEW

Sandro Gentile*, Ersilia Satta, Giuseppina Guarino, Carmine Romano, Felice Strollo

Obstructive Sleep Apnea (OSA) represents a significant global health burden, exacerbated by the ongoing obesity pandemic. This review evaluates the clinical impact of incretin-based therapies—specifically glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and the dual GIP/GLP-1 receptor agonist tirzepatide—on the management of OSA. By leveraging potent weight-loss mechanisms and potential weight-independent neuro-respiratory modulation, these pharmacologic agents have emerged as transformative tools in sleep medicine. Current clinical evidence demonstrates that tirzepatide significantly reduces the Apnea-Hypopnea Index (AHI) in patients with moderate-to-severe OSA and obesity, frequently leading to improved sleep quality and daytime alertness. Mechanistically, these therapies reduce upper airway collapsibility by decreasing visceral and pharyngeal adipose tissue, while potentially modulating brainstem centers responsible for respiratory rhythm stability. Despite these promising results, the chronic nature of metabolic diseases requires a long-term care model, as therapy discontinuation often leads to rapid weight regain and a resurgence of OSA severity. This review highlights that while these incretin-based therapies offer a robust, patient-centered alternative or adjunct to traditional mechanical ventilation, future research must focus on long-term cardiovascular outcomes and the integration of these drugs into multidisciplinary clinical pathways. Ultimately, semaglutide and tirzepatide redefine OSA management by effectively addressing the underlying metabolic pathophysiology.